Gabapentin is chemically, 1-(aminomethyl)-1-cyclohexane acetic acid, having the structure shown below:

Gabapentin is useful in treating epilepsy and various other cerebral disorders. It was first described by Warner-Lambert Co. in U.S. Pat. No. 4,024,175.
Several processes for the preparation of gabapentin are reported in the literature. U.S. Pat. No. 4,024,175 describes three methods to prepare gabapentin. All the methods result in gabapentin hydrochloride salt, which is converted to free gabapentin by treatment with a basic ion-exchange resin. U.S. Pat. No. 4,894,476 discloses a hydrated gabapentin which is prepared by liberating the free gabapentin base from its hydrochloride salt by pouring the salt solution onto a column of ion exchange resin like Amberlite IRA-68, eluting with deionised water and further work up to recover the hydrated form. U.S. Pat. No. 5,091,567 discloses the conversion of the gabapentin hydrochloride salt to gabapentin base by passing through a weakly basic anion exchanger. Gabapentin is manufactured in ton lot quantities and a preparative column chromatography is not convenient for applications on an industrial scale. It requires long time and results in a large volume of aqueous solution to be evaporated at low temperature, which makes the process cumbersome and uneconomical.
A process for the conversion of gabapentin hydrochloride to free gabapentin is described in the U.S. Pat. No. 6,255,526 B1. In this process, gabapentin hydrochloride is dissolved in a solvent such as ethyl acetate, in which free gabapentin is insoluble. An alkyl amine such as tributylamine is added to precipitate gabapentin, which is insoluble in the solvent and is recovered by filtration. Alkyl amine hydrochloride, formed in the reaction being soluble in the solvent, will remain in solution. Here, gabapentin is obtained as Form III and again has to be converted to Form II, which is the generic form. In addition to ethylacetate, the patent also mentions benzyl alcohol as a solvent and gives 43% yield of gabapentin (Table-1, Example 11). It is clear that only 43% gabapentin precipitates out from the solution and the remaining 57% remains in the solution. With only 43% yield, the process is uneconomical. Thus, benzyl alcohol is not a suitable solvent for this process.
U.S. Pat. No. 7,439,387 B2 describes the conversion of gabapentin hemisulphate salt to free gabapentin by treating with alkyl amines such as triethylamine or diisopropyl ethyl amine. In all these cases, the alkyl amines used are nonvolatile liquids and are difficult to remove, requiring repeated extractions.
U.S. Pat. No. 7,196,216 describes the conversion of gabapentin hydrochloride first to free base and then to its sulphate salt which is further treated with an inorganic base to obtain free gabapentin. The patent also describes the use of barium hydroxide as one of the inorganic bases which converts sulphate salt to free gabapentin. The process is cumbersome and involves a number of steps. Further use of barium hydroxide introduces toxic barium ions into the product at the final stages and requires extensive purification steps. Indian patent No. 186285 describes a process to convert gabapentin hydrochloride to gabapentin directly by treating with aqueous sodium hydroxide or other inorganic bases. U.S. Pat. Application No. US 2006/0149099 also describes a similar process and defines specific amounts of water and the alkali metal base to be used. Here, the reaction mixture is heated to 50-90° C., preferably at 60-70° C. This results in the formation of lactam to a significant extent and a method to recover lactam from the mother liquor is described (Mother liquor B, Example 1). Gabapentin obtained by these methods show high amounts of chloride, which is mainly from sodium chloride formed during neutralization with sodium hydroxide. Extensive purification steps are required to remove the chlorides.
Thus there is a need for a good process to convert gabapentin acid salt to free gabapentin which is free from anionic and other impurities.